Classical models of GHR activation suggest that GH binds sequentially to two GHR molecules, leading to receptor dimerization and activation. More recently, evidence from FRET, BRET, Co-IP (Brown et al. 2005) and molecular simulations (Poger & Mark 2010) suggest that dimerization occurs before ligand binding, and that activation is a consequence of conformational changes caused by ligand binding, namely a relative rotation of the receptor dimer so that the catalytic domains of JAK2 molecules bound to the cytoplasmic tails are brought into close proximity and are consequently able to phosphorylate each other (Rowlinson et al. 2008). Realignment of the receptor subunits and consequent JAK2 activation is supported by crystal structures of the related erythropoietin receptor (Livnah et al. 1999); similar proposals have been made for many receptors, including the prolactin and erythropoietin receptors (Brooks & Waters 2010).